Zileuton ((±)-1-(1-benzo[b]thien-2-ylethyl)-1-hydroxyurea) is the active pharmaceutical ingredient in ZYFLO™, which is currently used as a treatment for asthma. ZYFLO™ is the only FDA approved asthma treatment that inhibits 5-lipoxygenase activity. 5-Lipoxygenase is responsible for the first enzymatic step in the production of leukotrienes, a family of inflammatory mediators that can trigger asthma symptoms. In addition to asthma, leukotrienes have been shown to play a role in other diseases including rheumatoid arthritis, allergic rhinitis, acne, atherosclerosis, aortic aneurysm, sickle cell disease, nasal polyposis and inflammatory bowel disease, among others. Accordingly, compounds which inhibit lipoxygenase activity are useful in the treatment and/or prevention of such diseases. Because zileuton selectively inhibits the activity of 5-lipoxygenase, it may have broader therapeutic utility than other leukotriene inhibitors.
ZYFLO is a mixture of R(+) and S(−) enantiomers of zileuton. (+)-R-zileuton is a stereoisomer of zileuton, where R denotes the absolute configuration of the molecule about its chiral center and (+) denotes the sign of rotation of plane-polarized light by the compound. Pharmaceutically active agents often exist in two or more crystalline forms that have different key physical and pharmaceutical properties including hygroscopicity, solubility, storage stability, density, hardness, flow properties and bioavailability. Crystalline forms with optimal aforementioned properties are desirable for drug production and therapeutic application.